Comparison of rat liver response to coumarin administered in vivo versus in vitro

1964 ◽  
Vol 206 (1) ◽  
pp. 229-238 ◽  
Author(s):  
Judith G. Pool ◽  
C. F. Borchgrevink
Keyword(s):  
Amino Acid ◽  
Oxidative Phosphorylation ◽  
Vitamin K ◽  
Inhibitory Effect ◽  
Factor Vii ◽  
General Effect ◽  
Liver Slices ◽  
Cell Energy

Warfarin added to incubated liver slices inhibits the synthesis of factor VII (proconvertin) in proportion to the log of its concentration; surprisingly, it has the same inhibitory effect on the transport and incorporation of amino acid into protein of the liver slices. This latter finding seems to support the frequently proposed concept that vitamin K has a role in oxidative phosphorylation and that coumarin compounds, by antagonizing vitamin K, uncouple oxidative phosphorylation and thus have a general effect on cell energy supply. However, when we studied the liver of rats depleted of vitamin K the same effect was not seen. Liver slices from such animals produced little factor VII but they incorporated amino acid at the normal rate. Furthermore, administration of warfarin in vivo had the same result as vitamin K depletion: a fall in circulating prothrombin complex but no decrease in either labeling of plasma proteins by intravenous C14-amino acid or incorporation of amino acid into subsequently excised liver slices. There is thus a striking discrepancy between the action of warfarin administered in vitro and that administered in vivo.

Deficient synthesis of factor VII by liver tissue of fetal and newborn rats

1960 ◽  
Vol 199 (1) ◽  
pp. 139-142 ◽  
Author(s):  
Gerold M. Grodsky ◽  
Mona Kropatkin ◽  
Judith G. Pool
Keyword(s):  
Vitamin K ◽  
Fetal Liver ◽  
Fetal Tissue ◽  
Factor Vii ◽  
Clotting Factor ◽  
Adult Tissue ◽  
Adult Rats ◽  
Liver Slices

The deficiency of circulating factor VII in the newborn human being was confirmed for the newborn rat and its etiology studied. The ability of liver slices from fetal, newborn and adult rats to synthesize factor VII in vitro was compared under standard conditions. Fetal tissue had about 1/20 and newborn tissue about 1/3 the capacity of adult tissue to form this factor. Although a deficiency of vitamin K has been considered the cause of the clotting factor deficiencies at birth, supplementation of the rat tissue, either with vitamin K added to the liver slices in vitro or vitamin K given to prepartum mother rats in vivo, resulted in only minor improvement of the synthetic rate. Extracts of fetal liver were studied for the presence of an inhibitor of factor VII synthesis and extracts of adult tissue for the presence of a stimulator, but neither could be detected. It was concluded that a functional immaturity of liver enzyme systems involved in synthesis of factor VII exists at birth.

NEGATIVE EFFECTS OF VITAMIN K PREPARATIONS ON GLUCURONYL TRANSFERASE ACTIVITY

PEDIATRICS ◽  
1967 ◽  
Vol 40 (6) ◽  
pp. 993-999
Author(s):  
Barbara Jones
Keyword(s):  
Vitamin K ◽  
Inhibitory Effect ◽  
Water Soluble ◽  
In Vivo Studies ◽  
Transferase Activity ◽  
Negative Effects ◽  
Glucuronyl Transferase ◽  
Glucuronide Conjugation

In vitro studies using a mouse liver microsome system failed to demonstrate that menadiol sodium diphosphate, menadione sodium bisulfite, or phytonadione enhanced or inhibited the quantity of ortho-aminophenol glucuronide produced. In vivo studies in young rats with these vitamin K analogues also failed to show an effect on glucuronide conjugation. Based on this data, it is concluded that the hyperbilirubinemia seen in prematures after large doses of water-soluble vitamin K analogues is probably not due to an inhibitory effect of glucuronyl transferase. The evidence suggesting that it may be due in part to hemolysis is briefly reviewed.

scholarly journals Characterization of the inhibition of tissue factor in serum

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 150-155 ◽  
Author(s):  
GJ Jr Broze ◽  
JP Miletich
Keyword(s):  
Tissue Factor ◽  
Factor Viia ◽  
Factor Xa ◽  
Inhibitory Effect ◽  
Factor Vii ◽  
Factor X ◽  
Human Hepatoma Cells ◽  
Proteolytic Activation

Tissue factor (TF) is a lipoprotein cofactor that markedly enhances the proteolytic activation of factors IX and X by factor VIIa. The functional activity of TF is inhibited by serum in a time- and temperature-dependent fashion. The inhibitory effect is also dependent on the presence of calcium ions and can be reversed by calcium chelation (EDTA) and dilution, thus excluding direct proteolytic destruction of TF as the mechanism for inhibition. Using crude TF, serum immunodepleted of factor VII, and serum depleted of the vitamin K- dependent coagulation factors by BaSO4 absorption, it is shown that TF factor inhibition requires the presence of VII(a), X(a), and an additional moiety contained in barium-absorbed serum. When each of the other required components were at saturating concentrations, half- maximal inhibition of TF occurred in reaction mixtures containing 2% (vol/vol) of TF at a factor VII(a) concentration of 4 ng/mL (80 pmol/L), a factor X concentration of 50 ng/mL (850 pmol/L), and a concentration of barium-absorbed serum of 2.5% (vol/vol). Catalytically active factor Xa appeared to be required for the generation of optimal TF inhibition. The results are consistent with the conclusions of Hjort that barium-absorbed serum contains a moiety that inhibits the VIIa- Ca2+-TF complex. The role of factor X(a) in the generation of the inhibitory phenomenon remains to be elucidated. The inhibitor present in serum (plasma) may in part be produced by the liver in vivo since cultured human hepatoma cells (HepG2) secrete this inhibitory activity in vitro.

Amino acids in the rat intestinal lumen regulate their own absorption from a distant intestinal site

2009 ◽  
Vol 297 (2) ◽  
pp. G292-G298 ◽  
Author(s):  
Fadi H. Mourad ◽  
Kassem A. Barada ◽  
Carmen Khoury ◽  
Tamim Hamdi ◽  
Nayef E. Saadé ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Inhibitory Effect ◽  
Intestinal Lumen ◽  
Jejunal Segment ◽  
Subdiaphragmatic Vagotomy ◽  
Regulatory Loop ◽  
Dependent Transport

Intestinal nutrient transport is altered in response to changes in dietary conditions and luminal substrate level. It is not clear, however, whether an amino acid in the intestinal lumen can acutely affect its own absorption from a distant site. Our aim is to study the effect of an amino acid present in rat small intestinal segment on its own absorption from a proximal or distal site and elucidate the underlying mechanisms. The effect of instillation of alanine (Ala) in either jejunum or ileum on its own absorption at ileal or jejunal level was examined in vivo. The modulation of this intestinal regulatory loop by the following interventions was studied: tetrodotoxin (TTX) added to Ala, subdiaphragmatic vagotomy, chemical ablation of capsaicin-sensitive primary afferent (CSPA) fibers, and IV administration of calcitonin gene-related peptide (CGRP) antagonist. In addition, the kinetics of jejunal Ala absorption and the importance of Na+-dependent transport were studied in vitro after instilling Ala in the ileum. Basal jejunal Ala absorption [0.198 ± 0.018 μmol·cm−1·20 min−1 (means ± SD)] was significantly decreased with the instillation of 20 mM Ala in the ileum or in an adjacent distal jejunal segment (0.12 ± 0.015; P < 0.0001 and 0.138 ± 0.014; P < 0.002, respectively). Comparable inhibition was observed in the presence of proline in the ileum. Moreover, basal Ala absorption from the ileum (0.169 ± 0.025) was significantly decreased by the presence of 20 mM Ala in the jejunum (0.103 ± 0.027; P < 0.01). The inhibitory effect on jejunal Ala absorption was abolished by TTX, subdiaphragmatic vagotomy, neonatal capsaicin treatment, and CGRP antagonism. In vitro studies showed that Ala in the ileum affects Na+-mediated transport and increases Km without affecting Vmax. Intraluminal amino acids control their own absorption from a distant part of the intestine, by affecting the affinity of the Na+-mediated Ala transporter, through a neuronal mechanism that involves CSPA and CGRP.

scholarly journals Characterization of the inhibition of tissue factor in serum

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 150-155 ◽  
Author(s):  
GJ Jr Broze ◽  
JP Miletich
Keyword(s):  
Tissue Factor ◽  
Factor Viia ◽  
Factor Xa ◽  
Inhibitory Effect ◽  
Factor Vii ◽  
Factor X ◽  
Human Hepatoma Cells ◽  
Proteolytic Activation

Abstract Tissue factor (TF) is a lipoprotein cofactor that markedly enhances the proteolytic activation of factors IX and X by factor VIIa. The functional activity of TF is inhibited by serum in a time- and temperature-dependent fashion. The inhibitory effect is also dependent on the presence of calcium ions and can be reversed by calcium chelation (EDTA) and dilution, thus excluding direct proteolytic destruction of TF as the mechanism for inhibition. Using crude TF, serum immunodepleted of factor VII, and serum depleted of the vitamin K- dependent coagulation factors by BaSO4 absorption, it is shown that TF factor inhibition requires the presence of VII(a), X(a), and an additional moiety contained in barium-absorbed serum. When each of the other required components were at saturating concentrations, half- maximal inhibition of TF occurred in reaction mixtures containing 2% (vol/vol) of TF at a factor VII(a) concentration of 4 ng/mL (80 pmol/L), a factor X concentration of 50 ng/mL (850 pmol/L), and a concentration of barium-absorbed serum of 2.5% (vol/vol). Catalytically active factor Xa appeared to be required for the generation of optimal TF inhibition. The results are consistent with the conclusions of Hjort that barium-absorbed serum contains a moiety that inhibits the VIIa- Ca2+-TF complex. The role of factor X(a) in the generation of the inhibitory phenomenon remains to be elucidated. The inhibitor present in serum (plasma) may in part be produced by the liver in vivo since cultured human hepatoma cells (HepG2) secrete this inhibitory activity in vitro.

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

Oxytocin analogues with non-coded amino acid residues in position 8: [8-Neopentylglycine]oxytocin and [8-cycloleucine]oxytocin

1987 ◽  
Vol 52 (9) ◽  
pp. 2317-2325 ◽  
Author(s):  
Jan Hlaváček ◽  
Jan Pospíšek ◽  
Jiřina Slaninová ◽  
Walter Y. Chan ◽  
Victor J. Hruby
Keyword(s):  
Amino Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
The Other ◽  
Amino Acid Residues ◽  
Phase Synthesis ◽  
Other Hand ◽  
Fragment Condensation

[8-Neopentylglycine]oxytocin (II) and [8-cycloleucine]oxytocin (III) were prepared by a combination of solid-phase synthesis and fragment condensation. Both analogues exhibited decreased uterotonic potency in vitro, each being about 15-30% that of oxytocin. Analogue II also displayed similarly decreased uterotonic potency in vivo and galactogogic potency. On the other hand, analogue III exhibited almost the same potency as oxytocin in the uterotonic assay in vivo and in the galactogogic assay.

Synthesis of Fragments of the Vasoactive Intestinal Peptide (VIP) and Analysis of Their Residual Biological Activities

1995 ◽  
Vol 60 (7) ◽  
pp. 1229-1235 ◽  
Author(s):  
Ivana Zoulíková ◽  
Ivan Svoboda ◽  
Jiří Velek ◽  
Václav Kašička ◽  
Jiřina Slaninová ◽  
...  
Keyword(s):  
Amino Acid ◽  
Biological Activities ◽  
Residual Activity ◽  
Detailed Examination ◽  
Amino Acid Residues ◽  
Linear Peptide ◽  
Zone Electrophoresis ◽  
Capillary Zone

The vasoactive intestinal (poly)peptide (VIP) is a linear peptide containing 28 amino acid residues, whose primary structure indicates a low metabolic stability. The following VIP fragments, as potential metabolites, and their analogues were prepared by synthesis on a solid: [His(Dnp)1]VIP(1-10), VIP(11-14), [D-Arg12]VIP(11-14), [Lys(Pac)15,21,Arg20]VIP(15-22), and VIP(23-28). After purification, the peptides were characterized by amino acid analysis, mass spectrometry, RP HPLC, and capillary zone electrophoresis. In some tests, detailed examination of the biological activity of the substances in vivo and in vitro gave evidence of a low, residual activity of some fragments, viz. a depressoric activity in vivo for [His(Dnp)1]VIP(1-10) and a stimulating activity for the release of α-amylase in vitro and in vivo for [Lys(Pac)15,21,Arg20]VIP(15-22) and VIP(23-28).

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